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1.  Diagnostic value of contrast enhanced ultrasound for splenic artery complications following acute pancreatitis 
AIM: To assess the value of contrast-enhanced ultrasound (CEUS) in diagnosing splenic artery complications (SACs) after acute pancreatitis (AP).
METHODS: One hundred and eighteen patients with AP were enrolled in the study. All patients were examined by CEUS and contrast-enhanced computed tomography (CECT). CECT was accepted as a gold standard for the diagnosis of SACs in AP. The diagnostic accuracy of splenic CEUS and pancreatic CEUS was compared with that of CECT. Splenic infarction was the diagnostic criterion for splenic artery embolism and local dysperfusion of the splenic parenchyma was the diagnostic criterion for splenic arterial stenosis. The incidence of splenic sub-capsular hemorrhage, splenic artery aneurysms, and splenic rupture was all lower than that of SACs.
RESULTS: Nine patients were diagnosed as having SACs after AP by CECT among the 118 patients. The patients with SACs were diagnosed with severe acute pancreatitis (SAP). Among them, 6 lesions were diagnosed as splenic artery embolism, 5 as splenic artery aneurysms, and 1 as splenic arterial stenosis. No lesion was diagnosed by pancreatic CEUS and 5 lesions were diagnosed by splenic CEUS. By splenic CEUS, 4 cases were diagnosed as splenic artery embolism and 1 as splenic arterial stenosis. The accuracy of splenic CEUS in diagnosis of SACs in SAP was 41.7% (5/12), which was higher than that of pancreatic CEUS (0%).
CONCLUSION: Splenic CEUS is a supplementary method for pancreatic CEUS in AP patients, which can decrease missed diagnosis of SACs.
doi:10.3748/wjg.v20.i4.1088
PMCID: PMC3921534  PMID: 24574783
Acute pancreatitis; Severe acute pancreatitis; Contrast enhanced ultrasound; Splenic artery complications; Splenic contrast-enhanced computed tomography
2.  Coumarin-based Inhibitors of Bacillus anthracis and Staphylococcus aureus Replicative DNA Helicase: Chemical Optimization, Biological Evaluation, and Antibacterial Activities 
Journal of medicinal chemistry  2012;55(24):10896-10908.
The increasing prevalence of drug-resistant bacterial infections demands the development of new antibacterials that are not subject to existing mechanisms of resistance. Previously, we described coumarin-based inhibitors of an underexploited bacterial target, namely, the replicative helicase. Here we report the synthesis and evaluation of optimized coumarin-based inhibitors with 9–18-fold increased potency against S. aureus (Sa) and B. anthracis (Ba) helicases. Compounds 20 and 22 provided the best potency, with IC50 values of 3 and 1 µM, respectively, against the DNA duplex strand-unwinding activities of both B. anthracis and S. aureus helicases without affecting the single strand DNA-stimulated ATPase activity. Selectivity index (SI = CC50/MIC) values against S. aureus and B. anthracis for compound 20 were 33 and 66 and for compound 22 were 20 and 40, respectively. In addition, compounds 20 and 22 demonstrated potent antibacterial activity against multiple ciprofloxacin-resistant MRSA strains with MIC values ranging between 0.5–4.2 µg/mL.
doi:10.1021/jm300922h
PMCID: PMC3531573  PMID: 23231076
3.  Development and Application of a Cellular, Gain-of-Signal, Bioluminescent Reporter Screen for Inhibitors of Type II Secretion in Pseudomonas aeruginosa and Burkholderia pseudomallei 
Journal of biomolecular screening  2011;16(7):694-705.
The type II secretion (T2S) system in Gram-negative bacteria is comprised of the Sec and Tat pathways for translocating proteins into the periplasm and an outer membrane secretin for transporting proteins into the extracellular space. To discover Sec/Tat/T2S pathway inhibitors as potential new therapeutics, we used a Pseudomonas aeruginosa bioluminescent reporter strain responsive to SecA depletion and inhibition to screen compound libraries and characterize the hits. The reporter strain placed a luxCDABE operon under regulation of a SecA depletion-responsive up-regulated promoter in a secA deletion background complemented with an ectopic lac-regulated secA copy. Bioluminescence was indirectly proportional to the IPTG concentration and stimulated by azide, a known SecA ATPase inhibitor. A total of 96 compounds (0.1% of 73,000) were detected as primary hits due to stimulation of luminescence with a z-score ≥5. Direct secretion assays of the 9 most potent hits, representing 5 chemical scaffolds, revealed that they do not inhibit SecA-mediated secretion of β-lactamase into the periplasm, but do inhibit T2S-mediated extracellular secretion of elastase with IC50 values from 5 – 25 μM. In addition, 7 of the 9 compounds also inhibited the T2S-mediated extracellular secretion of phospholipases C by P. aeruginosa and of protease activity by Burkholderia pseudomallei.
doi:10.1177/1087057111408605
PMCID: PMC3195541  PMID: 21602485
P. aeruginosa; type II secretion; high throughput screening; inhibitors
4.  A High-Throughput, Homogeneous, Bioluminescent Assay for Pseudomonas aeruginosa Gyrase Inhibitors and Other DNA Damaging Agents 
Journal of biomolecular screening  2007;12(6):855-864.
A homogeneous, sensitive, cellular bioluminescent high throughput screen was developed for inhibitors of gyrase and other DNA damaging agents in Pseudomonas aeruginosa. The screen is based on a Photorhabdus luminescens luciferase operon transcriptional fusion to a promoter that responds to DNA damage caused by reduced gyrase levels and fluoroquinolone inhibition. This reporter strain is sensitive to levels of ciprofloxacin as low as ¼-MIC with Z’ scores above 0.5, indicating the assay is suitable for high-throughput screening. This screen combines the benefits of a whole cell assay with a sensitivity and target specificity superior to those of traditional cell-based screens for inhibitors of viability or growth. In duplicate pilot screens of 2,000 known bioactive compounds, 13 compounds generated reproducible signals ≥50% of that of the control (ciprofloxacin at ¼-MIC) using bioluminescence readings after 7h of incubation. Ten are fluoroquinolones known to cause accumulation of cleaved DNA-enzyme complexes in bacterial cells; the other three are known to create DNA adducts. Therefore, all 13 hits inhibit DNA synthesis, but by a variety of different DNA damaging mechanisms. This convenient, inexpensive screen will be useful for rapidly identifying DNA gyrase inhibitors and other DNA damaging agents, which may lead to potent new anti-bacterials.
doi:10.1177/1087057107304729
PMCID: PMC2561246  PMID: 17644773
P. aeruginosa; gyrase; high throughput screen; luciferase

Results 1-4 (4)